Lipoxygenase Inhibitory Activity Research Articles

Green Synthesis of Thiazolidine-2,4-dione Derivatives and Their Lipoxygenase Inhibition Activity With QSAR and Molecular Docking Studies.

Thiazolidinediones are five-membered, heterocyclic compounds that possess a number of pharmacological activities such as antihyperglycemic, antitumor, antiarthritic, anti-inflammatory, and antimicrobial. Conventional methods for their synthesis are often environmentally unacceptable due to the utilization of various catalysts and organic solvents. In this study, deep eutectic solvents were used in the synthesis of thiazolidinedione derivatives that acted as both solvents and catalysts. Initially, a screening of 20 choline chloride-based deep eutectic solvents for thiazolidinedione synthesis, via Knoevenagel condensation, was performed in order to find the most suitable solvent. Deep eutectic solvent, choline chloride, N-methylurea, was proven to be the best for further synthesis of 19 thiazolidinedione derivatives. Synthesized thiazolidinediones are obtained in yields from 21.49% to 90.90%. The synthesized compounds were tested for the inhibition of lipid peroxidation as well as for the inhibition of soy lipoxygenase enzyme activity. The antioxidant activity of the compounds was also determined by the ABTS and DPPH methods. Compounds showed lipoxygenase inhibition in the range from 7.7% to 76.3%. Quantitative structure–activity relationship model (R 2 = 0.88; Q 2 loo = 0.77; F = 33.69) for the inhibition of soybean lipoxygenase was obtained with descriptors Mor29m, G2u, and MAXDP. The molecular docking confirms experimentally obtained results, finding the binding affinity and interactions with the active sites of soybean LOX-3.

The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer's Disease In Vitro.

Alzheimer’s disease (AD) is a multifactorial disorder strongly involving the formation of amyloid-β (Aβ) oligomers, which subsequently aggregate into the disease characteristic insoluble amyloid plaques, in addition to oxidative stress, inflammation and increased acetylcholinesterase activity. Moreover, Aβ oligomers interfere with the expression and activity of Glycogen synthase kinase-3 (GSK3) and Protein kinase B (PKB), also known as AKT. In the present study, the potential multimodal effect of two synthetic isatin thiosemicarbazones (ITSCs), which have been previously shown to prevent Aβ aggregation was evaluated. Both compounds resulted in fully reversing the Aβ-mediated toxicity in SK-NS-H cells treated with exogenous Aβ peptides at various pre-incubation time points and at 1 μM. Cell survival was not recovered when compounds were applied after Aβ cell treatment. The ITSCs were non-toxic against wild type and 5xFAD primary hippocampal cells. They reversed the inhibition of Akt and GSK-3β phosphorylation in 5xFAD cells. Finally, they exhibited good antioxidant potential and moderate lipoxygenase and acetylcholinesterase inhibition activity. Overall, these results suggest that isatin thiosemicarbazone is a suitable scaffold for the development of multimodal anti-AD agents.

Discovery of benzothiazole-based thiazolidinones as potential anti-inflammatory agents: anti-inflammatory activity, soybean lipoxygenase inhibition effect and molecular docking studies

ABSTRACT Despite the greatest achievement in the development of anti-inflammatory agents in the last two decades, the current clinical drugs suffer from a variety of complications in community settings and hospital. There is still an urgent need to design novel molecules with better safety profile and with different molecular targets from those in current clinical use. The aim of this research was to discover a series of benzothiazole-based thiazolidinones with lipoxygenase (LOX) inhibitory activity as a mechanism of anti-inflammatory action. Carrageenan-induced mouse foot paw oedema assay was carried out to determine the anti-inflammatory activity, while LOX inhibition was examined through the conversion of sodium linoleate to 13-hydroperoxylinoleic acid. Molecular docking studies were performed using AutoDock 4.2 software. The anti-inflammatory activity of the title compounds was determined in a range of 18.4%-69.57%, where compound #3 was found to be the most potent (69.57%) and also to be more active than the reference drug indomethacin (47%). Moreover, compound #3 showed the highest LOX inhibitory activity with IC50 of 13 μM being less potent to that of the reference NDGA (IC50 = 1.3 μM). Compound #3 has been identified as lead compound for further modification in an attempt to improve anti-inflammatory and LOX inhibitory activities.

Pharmacological evaluation of the hypoglycemic and anti- Alzheimer’s activities of aerial parts of Breynia distachia (Phyllanthaceae)

Purpose: To determine the cytotoxic, bronchorelaxant, spasmolytic, antidiabetic, α-glucosidase, acetylcholinesterase, butyrylcholinesterase, α-chymotrypsin and lipoxygenase inhibitory attributes of methanol and dichloromethane extracts of the aerial parts of Breynia distachia.Methods: The dichloromethane and methanol extracts of the aerial parts of the plant were prepared by maceration. Various ex vivo assays were employed, such as the brine shrimp lethality assay, lipoxygenase inhibitory activity assay, α-glucosidase inhibitory assay and α-chymotrypsin assay, as well as assays to assess the spasmolytic and bronchorelaxant activity. Meanwhile, the hypoglycaemic effect were analysed using an alloxan-induced diabetic model in Wistar albino rats.Results: The methanol extract (aerial) showed significant (p ≤ 0.05) cytotoxicity towards brine shrimp larvae at concentrations of 10, 100 and 1,000 μg/mL, respectively, whereas the dichloromethane extract (aerial) of the plant showed non-significant (p ≥ 0.05) results. The methanol extract (aerial parts) also demonstrated significant (p ≤ 0.05) α-glucosidase inhibitory activity and lipoxygenase inhibitory activity, with IC50 (half-maximal inhibitory concentration) values of 40.37 ± 5.29 μg/mL and 132.9 ± 0.33 μg/mL, respectively, while the dichloromethane extract exhibited significant (p ≤ 0.05) α-glucosidase inhibitory activity, with an IC50 value of 135.43 ± 8.29 μg/mL. An in vivo antidiabetic model showed that the administration of 150 and 300 mg/kg methanol extract of the aerial parts significantly (p ≤ 0.05) lowered the blood glucose level in alloxan-induced diabetic rats compared to control (treated with water).Conclusion: Data from different in vitro and in vivo models suggest that the methanol extract (aerial parts) of B. distachia shows significant cytotoxic, bronchorelaxant, spasmolytic, antidiabetic and anti-Alzheimer’s activity Hence, these findings validate the folkloric use of B. distachia and highlight the need to further explore its medicinal potential and the phytoconstituents responsible for its pharmacological actions.

Phytochemical content, especially spermidine derivatives, presenting antioxidant and antilipoxygenase activities in Thai bee pollens.

BackgroundBee pollen (BP) is full of useful nutrients and phytochemicals.Its chemical components and bioactivities depend mainly on the type of floral pollen.MethodsMonofloral BP from Camellia sinensis L., Mimosa diplotricha, Helianthus annuus L., Nelumbo nucifera, Xyris complanata, and Ageratum conyzoides were harvested. Crude extraction and partition were performed to yield solvent-partitioned extracts of each BP. Total phenolic content (TPC) was assayed by the Folin-Ciocalteu method, while the flavonoid content (FC) was measured by the aluminium chloride colorimetric method. Antioxidant capacity was measured by the (i) 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, (ii) 2,2’-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) scavenging activity and its Trolox equivalent antioxidant capacity (TEAC), and (iii) ferric reducing antioxidant power (FRAP). All samples were tested for lipoxygenase inhibitory (LOXI) activity. The most active sample was enriched by silica gel 60 column chromatography (SiG60-CC) and high performance liquid chromatography (HPLC), observing the chemical pattern of each fraction using thin layer chromatography. Chemical structure of the most active compound was analyzed by proton nuclear magnetic resonance and mass spectrometry.ResultsDichloromethane (DCM)-partitioned BP extracts of H. annuus L. and M. diplotricha (DCMMBP) showed a very high TPC, while DCMMBP had the highest FC. In addition, DCMMBP had the strongest DPPH and ABTS radical scavenging activities (as a TEAC value), as well as FRAP value. Also, DCMMBP (60 µg/mL) gave the highest LOXI activity (78.60 ± 2.81%). Hence, DCMMBP was chosen for further enrichment by SiG60-CC and HPLC. Following this, the most active fraction showed higher antioxidant andLOXI activities with an EC50 for DPPH and ABTS of 54.66 ± 3.45 µg/mL and 24.56 ± 2.99 µg/mL (with a TEAC value of 2,529.69 ± 142.16 µmole TE/g), respectively, and a FRAP value of 3,466.17 ± 81.30 µmole Fe2+/g and an IC50 for LOXI activity of 12.11 ± 0.36 µg/mL. Triferuloyl spermidines were revealed to be the likely main active components.ConclusionsTPC, FC, and spermidine derivatives played an important role in the antioxidant and antilipoxygenase activities in M. diplotricha bee pollen.

A comparative study of in vitro lipoxygenase inhibition and DPPH (1, 1-Diphenyl-2-Picrylhydrazyl) free radical scavenging activity of Silybum marianum and [Notobasis syriaca (L.) Cass.] Fruits

Silybum marianum and Notobasis Syriaca belong to the most widespread thorny plants in the Middle East, the Mediterranean, and large areas of Asia. Both plants are derived from the Asteraceae family. The aim of this study was to compare the phytochemical content of the two plants, the scavenging activity of free radicals, and to evaluate the anti-inflammatory activity of their fruit extracts in vitro. Methanol extracts of the fruits were prepared from both plants. The activity of scavenging free radicals was studied using DPPH, and the anti-inflammatory activity was investigated in-vitro using soybean lipoxygenase, in comparison with quercetin as standard. The qualitative phytochemical screening of the fruits showed that both plants contained flavonoids, and coumarins. Both plants showed negative results with alkaloids, saponins, and anthraquinone. The fruit extract from Notobasis Syriaca has the highest capacity to scavenge free radical DPPH (IC50=22.1 mcg/mL), and it has higher ability to inhibit soybean lipoxygenase in-vitro (IC50= 2.7 mcg/mL) than fruit extract from Silybum marianum (IC50= 9.8 mcg/mL). This study showed that Silybum marianum and Notobasis Syriaca have a high ability to scavenge free radicals; and that both plants possess anti-inflammatory properties.

Comparative Analysis of In Vitro Enzyme Inhibitory Activities and Phytochemicals from Platycladus orientalis (L.) Franco via Solvent Partitioning Method.

The extraction of plant bioactive compounds from Platycladus orientalis (L.) Franco remains a great challenge due to the different chemical groups. This study aimed to compare the bioactive compounds with enzyme inhibitory effect from P. orientalis via solvent partitioning method. Dried leaf samples were macerated and fractionated with six solvents of different polarities. The phenolic, flavonoid, tannin, saponin, alkaloid and pharmacological activities including anti-inflammatory, anti-diabetic, antioxidant and anti-glycation potential were compared across the six plant fractions. Toxicity assessment was performed with an in vivo brine shrimp model. The varying levels of bioactive compounds in ethyl acetate (phenolics, flavonoids), hexane (saponins, tannins) and chloroform (alkaloids) fractions clearly demonstrated the significant impact of solvent polarity on the extraction of bioactive compounds. The reducing potential (r = 0.67), IC50 of α-amylase inhibition (r = -0.71), IC50 of advanced glycation end-product inhibition (r = -0.93) and dicarbonyl compound inhibition (r = 0.57) in the plant fractions were correlated (p<0.05) with the flavonoids. Besides, the alkaloid, saponin and tannin were associated with cyclooxygenase-1 inhibitory activity. Principal component analysis confirmed that solvent polarity (23.9%) and plant extraction yield (37.1%) collectively contributed to 61% of bioactivity variation in P. orientalis. Among the six plant fractions, ethyl acetate fraction exhibited relatively high anti-inflammatory, anti-diabetic, antioxidant and anti-glycation potential while the non-toxic methanolic and aqueous fractions displayed optimal hyaluronidase and lipoxygenase inhibitory activities, respectively. The current study has identified semi-polar ethyl acetate fraction of P. orientalis as a good alternative source of bioactive compounds for future pharmaceutical product development.

A Novel Distachionate from Breynia distachia Treats Inflammations by Modulating COX-2 and Inflammatory Cytokines in Rat Liver Tissue.

Breynia distachia is a plant of genus Breynia belonging to family Phyllanthaceae. This study was conducted to isolate and examine the anti-inflammatory attributes of the roots of Breynia distachia. Methanol extract from roots were prepared by simple maceration. For phytochemical studies, isolation, purification, structure elucidation, metal analysis, total phenolic content, and solubility test were done by chromatographic and spectroscopic techniques. Anti-inflammatory activity was evaluated by cotton pallet edema model and carrageenan paw edema model, and antioxidant potential was evaluated by DPPH, FRAP, and ABTS antioxidants assays. Metal analysis of BD.Me revealed the presence of Na > Mg > K > Mn > Fe = Zn in respective order. Four phytochemicals such as gallic acid, quercetin, sinapic acid, and p-coumaric acid are found in Breynia distachia. Quercetin is present in relatively larger quantity, and shows antioxidant activity by reducing the ferric iron to ferrous iron. Novel distachionate shows high antioxidant activity in ABTS assay by reducing reactive oxygen species. Quantitative or qualitative analysis performed by HPLC indicates the ascending peaks or presence of secondary products (metabolites) respectively. Histopathology analysis of liver, spleen, heart, and kidney was done, revealing mild inflammations in spleen and liver, and no cytotoxicity in heart and kidney. Oral administration of BD.Me and ditachionate significantly inhibits the carrageenan and cotton pellet-induced paw edema in 1st and 2nd h with (ns = p > 0.05) than control. After 3rd, 4th, 5th, and 6th h, BD.Me and ditachionate showed inhibition of paw edema in a highly significant (*** = p < 0.001) manner as compared to control. In cotton-pellet edema model, distachionate shows a %inhibition of 57.3% at a dose level of 5 mg/kg. Docking values obtained from distachionate-COX-2 complex suggest a potent inhibitor evaluated for this protein. The distachionate shows effective anti-inflammatory activity. Methanol extracts of roots showed significant lipoxygenase inhibitory activity by IC50 values of 155.7 ± 0.55 and 132.9 ± 0.33 μg/mL. Data from various in vitro and in vivo models suggest that novel distachionate isolated from Breynia distachia shows strong antioxidant and anti-inflammatory activities; it should be further studied for the exploration of its medicinal potential.

Effect of high‐pressure CO2 injection on the physicochemical properties and lipoxygenase activity of extruded rice bran

AbstractBackground and ObjectivesRice bran is rich in nutrients but not very stable and available, so extrusion of it broadens its utilization value. The objective was to investigate the effects of extrusion parameter variables on the physicochemical properties and lipoxygenase activity of extruded rice bran. The extrusion parameter variables were set as extrusion temperature (80, 90, 110, 140°C); CO2 injection, and no CO2 injection; screw speed (200, 300 rpm).FindingsCO2 injection significantly affected the expansion characteristics and lipoxygenase activity of extruded rice bran. It better inhibits lipoxygenase activity and at a fixed screw speed of 200 rpm, the bulk density of extruded rice bran with CO2 injection was higher than that of conventional extrusion. After extrusion, the soluble dietary fiber content was significantly increased in the extruded samples compared with the raw material. In contrast, the content of dietary fiber was not significantly affected by CO2 injection.ConclusionsCompared with the conventional extrusion method, the CO2‐injected extrusion has significant effects on the expansion characteristics and nutritional composition. Extrusion with CO2 injection can reduce lipoxygenase activity more effectively.Significance and NoveltyThe results prove that CO2 extrusion can inhibit the lipoxygenase activity, and change the physicochemical properties of rice bran compared with conventional extrusion. It provides a basis for the application of CO2 as a medium in extruded rice bran food and a new process for processing rice bran by‐products.

High-pressure carbon dioxide treatment alleviates browning development by regulating membrane lipid metabolism in fresh-cut lettuce

The influence of high-pressure carbon dioxide (HPCD) treatment on the browning of fresh-cut lettuce was investigated during storage at 4 °C. The browning degree, color, weight loss, browning-related enzymes, and components related to membrane lipid metabolism of fresh-cut lettuce were assessed during storage. The results showed that HPCD treatment slowed down the browning of fresh-cut lettuce. Polyphenol oxidase activity and total phenolic content of HPCD-treated group were reduced by 53.50% and 74.63%, respectively. In addition, HPCD treatment inhibited lipoxygenase activity and delayed membrane lipid peroxidation, thus decreasing PAL's stimulation by membrane lipid peroxidation products and further reducing the synthesis of phenolic. On the other hand, HPCD treatment maintained the structural integrity of the cell membrane and prevented the cell membrane compartmentalization from being broken due to cell membrane breakage by inhibiting phospholipase D activity, which avoided the contact between enzyme and phenol and delayed the oxidative browning.

Plectranthus zeylanicus: A Rich Source of Secondary Metabolites with Antimicrobial, Disinfectant and Anti-Inflammatory Activities.

Plectranthus zeylanicus Benth is used in Sri Lankan folk medicine as a remedy for inflammatory conditions and microbial infections. Our previous investigations revealed potent 5-lipoxygenase (5-LO) inhibitory activity in lipophilic extracts of this plant, supporting its anti-inflammatory potential. In-depth studies on the antimicrobial activity have not been conducted and the bioactive ingredients remained elusive. As a continuation of our previous work, the present investigation was undertaken to evaluate the antimicrobial activity of different extracts of P. zeylanicus and to isolate and characterize bioactive secondary metabolites. Different organic extracts of this plant were analyzed for their antibacterial activity, and the most active extract, i.e., dichloromethane extract, was subjected to bioactivity-guided fractionation, which led to the isolation of 7α-acetoxy-6β-hydroxyroyleanone. This compound displayed strong antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of 62.5 µg/mL, and its disinfectant capacity was comparable to the potency of a commercial disinfectant. Moreover, 7α-acetoxy-6β-hydroxyroyleanone inhibits 5-LO with IC50 values of 1.3 and 5.1 µg/mL in cell-free and cell-based assays, respectively. These findings rationalize the ethnopharmacological use of P. zeylanicus as antimicrobial and anti-inflammatory remedy.

Different tea polyphenol treatments on lipid oxidation of scallop ( Argopecten irradians ) adductor muscle during hot air drying

This study investigated the effects of different tea polyphenol (TP) treatments (control, unmarinated, and marinated) on scallop adductor muscle lipid oxidation during hot air drying. Results showed that the marinated sample had the lowest peroxide value, thiobarbituric acid reactive substances, polyunsaturated fatty acids loss, free radical level, and lipoxygenase activity during drying, indicating that the marination process maximized the antioxidant effects of TP. These results were achieved by the distributing of TP on lipid oxidation site, effectively intercepting free radical chain reaction and inhibiting lipoxygenase activity. The significant loss of total phenolic content in the marinated sample confirmed this result. The control, unmarinated, and marinated sample lost 26.52%, 9.99%, and 6.46% of eicosapentaenoic acid and docosahexaenoic acid during drying, respectively, indicating that the marination more efficiently maintained its high nutritive value in terms of lipid. This study provided a more effective way of using TP to control lipid oxidation in seafood during drying. Novelty impact statement Marinated with TP improved its antioxidant effect during scallop drying. More than 26% of EPA + DHA lost in scallop adductor muscle, while less than 7% of EPA + DHA lost in marinated scallop adductor muscle during drying. Marinated with TP maintained the higher nutritive value of scallop during drying.

Nucleobase-Derived Nitrones: Synthesis and Antioxidant and Neuroprotective Activities in an In Vitro Model of Ischemia-Reperfusion.

Herein, we report the synthesis, antioxidant, and neuroprotective properties of some nucleobase-derived nitrones named 9a–i. The neuroprotective properties of nitrones, 9a–i, were measured against an oxygen-glucose-deprivation in vitro ischemia model using human neuroblastoma SH-SY5Y cells. Our results indicate that nitrones, 9a–i, have better neuroprotective and antioxidant properties than α-phenyl-N-tert-butylnitrone (PBN) and are similar to N-acetyl-L-cysteine (NAC), a well-known antioxidant and neuroprotective agent. The nitrones with the highest neuroprotective capacity were those containing purine nucleobases (nitrones 9f, g, B = adenine, theophylline), followed by nitrones with pyrimidine nucleobases with H or F substituents at the C5 position (nitrones 9a, c). All of these possess EC50 values in the range of 1–6 μM and maximal activities higher than 100%. However, the introduction of a methyl substituent (nitrone 9b, B = thymine) or hard halogen substituents such as Br and Cl (nitrones 9d, e, B = 5-Br and 5-Cl uracil, respectively) worsens the neuroprotective activity of the nitrone with uracil as the nucleobase (9a). The effects on overall metabolic cell capacity were confirmed by results on the high anti-necrotic (EC50′s ≈ 2–4 μM) and antioxidant (EC50′s ≈ 0.4–3.5 μM) activities of these compounds on superoxide radical production. In general, all tested nitrones were excellent inhibitors of superoxide radical production in cultured neuroblastoma cells, as well as potent hydroxyl radical scavengers that inhibit in vitro lipid peroxidation, particularly, 9c, f, g, presenting the highest lipoxygenase inhibitory activity among the tested nitrones. Finally, the introduction of two nitrone groups at 9a and 9d (bis-nitronas 9g, i) did not show better neuroprotective effects than their precursor mono-nitrones. These results led us to propose nitrones containing purine (9f, g) and pyrimidine (9a, c) nucleobases as potential therapeutic agents for the treatment of cerebral ischemia and/or neurodegenerative diseases, leading us to further investigate their effects using in vivo models of these pathologies.

Lipoxygenase Inhibitory Activity of Some Extracts Prepared from Flaxseed (Linum usitatissimumv L.)

Background: Lignans are biologically important phenolic compounds that exist in different levels of various plants; yet, flaxseed is one of the richest sources of such compounds. Lipoxygenase enzymes are associated with many inflammatory-related diseases such as arthritis, allergic asthma, psoriasis, cardiovascular disease, kidney disease, skin diseases, and neuropsychiatric disorders, as in Alzheimer's disease. Not only are these enzymes involved in many types of cancers, but they are also very crucial to find new LOX inhibitors to treat human diseases such as cancer or cardiovascular disease. Screening for lipoxygenase inhibitory activities of flaxseeds lignans extracts in various methods is reported in this work. Methods: Extracts of samples of flaxseeds (Linum usitatissmum) were prepared using the following methods: a- extraction with continuous stirring with 80% ethanol, b- extraction with a mixture of equal volumes of diethyl ether and ethyl acetate after direct acid hydrolysis, c- Extraction with 50% ethanol followed by alkaline hydrolysis. Total flavonoids, total phenolic of these extracts were compared. The scavenging potential of free radicals was determined using the DPPH method. The inhibitory potential against the lipoxygenase enzyme was determined by using the soybean lipoxygenase enzyme. Results: The highest phenolic content was in the extract prepared with ethanol 80% with continuous stirring, with phenolic content of (126.848 mg GAE /g). While the highest flavonoid was content in the extract prepared with a mixture of equal volumes of diethyl ether and ethyl acetate after direct acid hydrolysis, with flavonoid content reached (7.8 mg QE / g). Moreover, the scavenging potential of free radicals expressed in terms of IC50 (μg/ml) showed extraction with a mixture of equal volumes of diethyl ether and ethyl acetate after direct acid hydrolysis exhibited higher antioxidant capacity (IC50=22.257±0.095 μg/ml) followed by 80% ethanol extract. The median inhibitory concentration (IC50) was calculated according to the LOX enzyme inhibitory method. The IC50 value of a mixture of equal volumes of diethyl ether and ethyl acetate after direct acid hydrolysis extract of flaxseeds is 73.689±0.585 μg/ml. Conclusion: The mixture of equal volumes of diethyl ether and ethyl acetate extract after direct acid hydrolysis gives stronger scavenging potential of free radicals and lipoxygenase inhibitory effects than the other extracts in this study. Therefore, according to the results we got in our study, flaxseed extracts can be a potential source of novel therapeutics to treat many diseases related to the LOX enzyme.

Undescribed Anti-Inflammatory Thalysiaketides from Marine Sponge Clathria (Thalysias) vulpina (Lamarck, 1814).

Two undescribed polyketide-type compounds, thalysiaketide A and thalysiaketide B were isolated from a sponge of marine origin Clathria (Thalysias) vulpina (Lamarck, 1814). Thalysiaketide A exhibited significantly greater inhibitory potential against inflammatory 5-lipoxygenase (IC50 0.87 mM) and cyclooxygense-2 (IC50 0.93 mM) compared to those displayed by its thalysiaketide B analog (IC50 ≥1.05 mM). The 5-lipoxygenase inhibitory activity of thalysiaketide A was considerably superior to ibuprofen (standard, IC50 >4 mM). Higher degree of polar belongings (topological polar surface area 93.06) in conjunction with relatively lower docking parameters of thalysiaketide A with the aminoacyl residues of cyclooxygense-2 and 5-lipoxygenase (docking score -12.99 and -12.27 kcal/mol, respectively) recognized its prospective anti-inflammatory potential.

Monomeric octahedral bismuth(III) benzaldehyde-N1-alkyl thiosemicarbazones: Synthesis, characterization and biological properties

Due to their chemical and biological properties, the interest in thiosemicarbazones and their metal complexes is increasing day by day. In this study, the effect of the substituents at the N1 atoms of the thiosemicarbazones and the effect of halogen atoms on the type and biological properties of bismuth(III) complexes is investigated. The reactions of bismuth(III) halide with a series of benzaldehyde-N1-alkyl-thiosemicarbazones in 1:3 M ratio yield bismuth(III) halide complexes: {BiBr3(η1-S-Hbztsc)3} (1), {BiCl3(η1-S-Hbzmtsc)3} (2), {BiBr3(η1-S-Hbzmtsc)3} (3), {[BiCl3(η1-S-Hbzetsc)3].CH3OH} (4) and {BiBr3(η1-S-Hbzetsc)3} (5). Complexes 1–5 were characterized by a number of different spectroscopic methods. The crystal structures of complexes 1–5 and the free ligand benzaldehyde-N-methyl-thiosemicarbazone were determined by X-ray diffraction. Complexes 1–5 were tested for their in vitro cytotoxic activity against human breast adenocarcinoma (MCF-7) cell line. Complexes 1–5 showed low cytotoxic activity. The antibacterial activities of 1–5 and their free ligands against four strains bacteria of Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli have been examined. The results indicated that bismuth(III) complexes 1–5 are most active against E. coli and, among them, complex 4 exhibits the highest activity. Lipoxygenase (LOX) inhibitory activity of the bismuth(III) halide complexes 1–5 and the free ligands has been detected experimentally. The IC50 values indicate that bismuth(III) halide complexes 1–5 have a higher enzyme inhibition potential than free ligands and cisplatin.

In vitro Synthesis, Structure Elucidation, and Antioxidant Properties of Platinum(IV)-hydrazide Complexes: Molecular Modeling of Free- Hydrazides Suggested as Potent Lipoxygenase Inhibitor.

A combination of biologically active ligand and metal in one molecule may increase the activity and reduce the toxicity. In this study, the synthesis and characterization of platinum(IV) complexes with bioactive hydrazide ligands are discussed. Elemental analysis, conductivity measurements, and spectroscopic studies were used to elucidate the structure of complexes. Our study suggests that hydrazide ligands coordinate with Pt(IV) in a bidentate fashion. The platinum(IV) complexes have octahedral geometry with a metal to ligand ratio of 1:2. Hydrazide ligands were coordinated with central metal platinum(IV) by oxygen of carbonyl group and nitrogen of primary amine. Synthesized complexes exhibited variable DPPH radical scavenging and lipoxygenase inhibition activity. Furthermore, it is also found that Pt(IV)-hydrazide complexes are more potent superoxide and nitric oxide radical scavengers than their uncoordinated hydrazide ligands, while in the case of lipoxygenase enzyme inhibition, some of the free hydrazide ligands are more active than their respective Pt(IV) complexes. In silico docking technique explores molecular interactions of synthesized ligands in the active site of the lipoxygenase enzyme. Predicted docking energies are in good agreement with experimental data suggesting that in silico studies might be useful for the discovery of therapeutic candidates. Structure-function relationship demonstrates that the radical scavenging and enzyme inhibition activities of the Pt(IV) compounds are affected by the nature of the ligand, position of substituent, electronic and steric effects. However, electronic factors seem to play a more important role than other factors.

Chemical Composition and Lipoxygenase Inhibitory Activity of the Essential Oil of Alstonia Angustiloba

This study was aimed to investigate the chemica l compositions and lipoxygenase inhibitory activity of the essential oil from Alstonia angustiloba growing in Malaysia. The essential oils were obtained by hydrodistillation and fully characterized by gas chromatography and gas chromatography-mass spectrometry. Analysis of the A. angustiloba essential oil resulted in the identification of twenty-five chemical components, attributed 90.8% of the total oil. The most abundant components of A. angustiloba oil were linalool (21.2%), 1,8-cineole (16.8%), α-terpineol (9.5%), terpinene-4-ol (8.5%), β-caryophyllene (6.2%), and caryophyllene oxide (5.2%). The essential oil displayed moderate activity towards lipoxygenase activity with IC50 value of 45.8 μg/mL.

In vitro pharmacological attributes and metabolite’s fingerprinting of Conocarpus lancifolius

Search for safe antioxidants and novel nutraceuticals urged to evaluate the antioxidant, anti-acetylcholine esterase and anti-lipoxygenase activity of various leaf extracts of Conocarpus lancifolius. Extraction was optimized from freeze dried plant extracts quenched with liquid nitrogen using water, ethanol, methanol, hexane, ethyl acetate and chloroform. Maximum extract yield, total phenolic contents and total flavonoid contents were obtained in case of ethanolic extraction. The highest 2,2-diphenyl-1-picrylhydrazylradical scavenging in terms of IC50 value of 55.26 µg/mL was observed for ethanolic leaf extract. The acetylcholine esterase and lipoxygenase inhibitory activities (IC50) were also observed for ethanolic extract. These findings for ethanolic extract were statistically significant when compared with other extracts (ρ&lt;0.05). The haemolytic % values indicated that all extracts were associated with very low or negligible toxicity. The epicatechin, isorhamnetin, rutin, scopoleptin, skimmianine, quercetin-3-O-α-rhamnoside, quercetin-3-O-β-glucoside, cornoside, creatinine, choline, pyruvic acid, α-hydroxybutyric acid, phyllanthin and hypophyllanthin were identified as major functional metabolites in ethanolic leaf extract of C. lancifolius by 1H-NMR. The identified metabolites were probably responsible for the pharmacological properties of C. lancifolius. The findings may be utilized as pharmacological leads for drug development and food fortification.

A new eudesmanolide from Tanacetum balsamita L. and biological activities of extracts

The ethyl acetate and methanol extracts from aerial parts of Tanacetum balsamita yielded a new derivative of 1-acetyl-erivanin, namely 1-acetyl-3-epi-erivanin (17), some known compounds, namely seventeen sesquiterpene lactones, five flavonoids, four coumarins, and a steroid. All extracts displayed antibacterial activity against test microorganisms except for Escherichia coli. The methanol (TBM) extract with an IC50 value of 0.180 mg/mL exhibited good antioxidant activity against DPPH radical while all extracts showed significant anti-inflammatory activity against lipoxygenase enzyme. The ethyl acetate (TBEA) extract presented moderate activity against α-glucosidase enzyme with an IC50 of 0.808 mg/mL. The highest total phenol content with 91.050 mg GAE/g extract was found in TBM. It is the first study on the isolation of secondary metabolites as well as 5-lipoxygenase and α-glucosidase inhibitory activity of T. balsamita growing in Turkey.